Authors: Parker A. Small, Jr., M.D. and Bradley S. Bender, M.D., University of Florida

Why does influenza virus variously eventuate in mild upper respiratory tract infection, bacterial pneumonia, or rapidly fatal virus pneumonia? Many factors are important: the depth of infection, competence of immunologic effectors - local antibody (secretory IgA) for preventing upper respiratory infection (URI), systematic antibody for preventing pneumonia, and cellular immunity for recovery from either.

Introduction and Learning Objectives

Until the advent of AIDS, influenza was the last uncontrolled pandemic killer of humans. One historic measure of influenza's potential lethality is that more people died in the 1918-19 pandemic than in World War I. In the United States, influenza currently causes more morbidity and mortality than AIDS. In nonpandemic years, 10,000 to 20,000 people die of influenza-related illness in the U.S. In pandemic years, such deaths can exceed 100,000; the morbidity, of course, far exceeds the mortality.

The influenza viruses are a group of RNA viruses designated as types A, B, and C. Type C may not be a true influenza virus and usually causes only mild or asymptomatic disease. Influenza B virus usually causes a minor illness, but it does have the potential to cause more severe disease in older persons. Influenza A virus, however, causes pandemics. The reason for the recurrent outbreaks is that the virus undergoes periodic antigenic shifts in its two outer membrane glycoproteins-hemagglutinin (H) and neuraminidase (N)-for example, from H1N1 to H2N2 in 1957 and from H2N2 to H3N2 in 1968, thus introducing a new virus into a population that has no protective serum antibody. No different subtypes of H and N have been identified for influenza B and C.

This module will describe syndromes caused by influenza virus and explain why some patients have only a mild upper respiratory tract infection, whereas others have a viral pneumonia that rapidly progresses to death. It will also examine host defense mechanisms against influenza and their implications for creation of more effective vaccines. It also covers practical treatment issues.

Influenza virus infection causes three syndromes (Figure 1):

• an uncomplicated rhinotracheitis
• a respiratory viral infection followed by bacterial pneumonia
• viral pneumonia

All three syndromes have incubation periods of one to two days. In the early stages, they are often clinically indistinguishable from many other viral infections. One distinguishing feature of influenza virus infection, present in a small percentage of patients, is very rapid onset of profound malaise. In as little as one or two minutes, patients who feel well may feel so tired that they can hardly move. The Centers for Disease Control has a nice diagram of the infection cycle of the influenza virus.

Case Studies

This learning module will introduce you to four case studies, all dealing with different members of the Smith family. Each case will present you with several questions; answers will be provided. A post-test is included for physicians interested in earning CME credit. There is no charge for credit.

Case Study #1
Case Study #2
Case Study #3
Case Study #4
Post-test

Additional Learning Materials

Summary of Uncomplicated Rhinotracheitis.

For more information on the role of IgG antibody, IgA antibody or cell-mediated immunity, click on Host Defense.

To better understand why the same viruses can cause lethal viral pneumonia in some people and only mild URI in others, click on Lethal in Some and Mild in Others.

For more information on vaccines, including a brief description of the authors new experimental approach, click on Vaccines.

Click here for information on Viral Infections Followed by Bacterial Pneumonia and Influenza Viral Pneumonia.

To find out why the vaccine needs to be changed each year, check here.

To find out why the virus causes pandemics every ten to forty years, check here.

For more information on drug therapy, click on influenza therapeutics.

Here is a copy of our Patient Information Sheet which can be printed and given to patients.

Flu-Related Links

Health Care Financing Administration
Influenza A Virus Replication
Influenza Bibliography
NIAID Fact Sheet

Let Us Know What You Think

We would like to hear what you think about this flu module. Email your comments to Dr. Timothy VanSusteren, Associate Dean for Continuing Medical Education. Be sure to tell us who you are, your title, and where you're from. We would like to know what you liked best, what changes we should make, and any other comments you may have. Feedback will help us to improve this site.

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